Project Summary (REWRITTEN) Community-associated methicillin-resistant S. aureus (CA-MRSA) is a major problem in urban areas, with illicit drug use, incarceration, unstable housing, and geographic area of residence each being associated with CA- MRSA risk. Using genomic sequencing, we have previously demonstrated that community networks may facilitate the spread of MRSA outside of households, and epidemiologic exposures, including residence in a high detainee release area, may serve as the basis for linkages between individuals colonized or infected with genetically similar MRSA strains. The extent to which jails facilitate MRSA transmission, both during incarceration and to the community at large, is unknown. Our preliminary data demonstrate a high proportion of individuals enter the jail already colonized with MRSA and jails then provide an opportunity for at-risk individuals to intermingle which may promote further spread of MRSA. As urban jails are characterized by high turnover and high recidivism, we speculate the jails may be one of the major drivers of MRSA spread from and back into urban communities. Despite the demonstrated risk associated with community settings, studies examining infection prevention for MRSA have been conducted almost exclusively in hospitals. It is unknown if transmission dynamics and risk factors for acquisition of MRSA in the community are the same as those that drive transmission in hospitals. Prior studies of sexually transmitted diseases have demonstrated that interventions in urban jails can have significant downstream benefits in the community and provide an opportunity to intervene with a difficult-to-reach population that often lacks access to medical care. We believe this type of intervention could be extended to MRSA and that molecular epidemiologic analysis would help to design and maximize the benefits of a community intervention. Funds are requested to examine the genomic epidemiology of MRSA in an urban community and to identify and characterize epicenters for MRSA spread. We will use existing MRSA clinical cultures from 2008-2018 and integrate genomic data from these isolates with geocoding, epidemiologic, detainee release, and US census data to test whether there are geographic areas at highest risk for MRSA spread. We will use spatial transmission modeling to identify rates of MRSA transmission within and between community areas and to test hypothetical interventions. The proposal has three aims: (1) Characterize the movement of MRSA over time to identify if there is differential risk for spread in various community areas, (2) Determine if community MRSA strains are genomically related to MRSA strains isolated from individuals incarcerated at the jail, and (3) Identify hotspots of MRSA spread in the community using population genomics modeling. This innovative project will be the first to track the spread of MRSA in a large urban area, with results highlighting populations and community areas that may be the best targets for prevention efforts. Because the study will explore well-documented disparities with CA-MRSA, our findings will be generalizable to other underserved populations, underscoring the public health importance.